Thrombosis Update最新文献

Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE). Acute PE is associated with significant morbidity and mortality. Hospital admission is a common cause of VTE.

We present a complex case of a young female patient who sustained a right tibial plateau fracture following a traumatic, hyperextension knee injury. The patient was admitted by the orthopaedic team for an open reduction and internal fixation and commenced on prophylactic low molecular weight heparin. Post-operatively, the patient became hypoxic, and computed tomography pulmonary angiogram confirmed bilateral large volume pulmonary emboli with evidence of right heart strain. Following review by the pulmonary embolism response team (PERT), the patient was stratified into an intermediate-high risk group, and received unfractionated heparin, however, remained tachycardic and hypoxic with rising lactate levels. Owing to relative contraindications to systemic thrombolysis, the patient underwent catheter-based thrombectomy and inferior vena cava filter placement. The patient improved dramatically over the course of her admission and was later discharged, asymptomatic from a cardiopulmonary standpoint. In hospitalised patients, early VTE risk assessment and prompt initiation of appropriate thromboprophylaxis are crucial in preventing hospital-acquired VTE (HAVTE). However, in instances of HAVTE in complex patients, a well-coordinated multidisciplinary PERT is necessary to consider alternative strategies for managing intermediate to high-risk PE.

Introduction

Pulmonary embolism (PE) probability assessment relies on clinical scoring systems, which have limitations for certain patient populations. We aimed to investigate the use of laboratory values for PE probability assessment.

Materials and methods

This retrospective single-center observational study included patients with suspected PE. Nineteen variables were examined. Logistic regression analysis adjusted for confounding factors was performed, and significant variables were used to develop a scoring method. Receiver operating characteristic (ROC) curves were used to detect PE and determine the optimal cutoff value. Well's scores were also estimated.

Results

The model achieved an accuracy of 84.6 %. Hypocapnia, fever, alkaline phosphatase (ALP), D-dimer, and lactate levels had predictive values. The slope was negative for hypocapnia, ALP, and lactate, and positive for fever and D-dimer levels. Fever, with an adjusted odds ratio (OR) of 1.995, received a score of 2 for values above the cutoff, whereas the remaining variables were assigned a score of 1. Patients with PE had significantly higher scores (mean ± SD: 2.07 ± 0.91) than those without PE (1.80 ± 1.13; P = 0.001). The area under the ROC curve was 0.585 (95 % confidence interval: 0.563–0.606; P = 0.001). Using a cutoff score of 1.5 based on the maximum Youden's index, the scoring system achieved a sensitivity of 73.1 % and specificity of 43.4 %. The Well's score demonstrated a sensitivity of 51.1 % and specificity of 75.1 %.

Conclusion

This study showed statistically significant laboratory values for the probability assessment of PE and the tentative scoring system (PAPEL score). Larger prospective multicenter studies are required to validate this scoring method in a wider population.

Introduction

Oral anticoagulant therapy comes at the cost of a significant bleeding risk. However, it is hard to predict which patients are at risk of major bleeding. Previously we found associations of Calibrated Automated Thrombinography (CAT) parameters obtained in the presence of TIX-5 (an inhibitor of the FV activation by FXa), and plasma levels of TFPIα, γ’-fibrinogen and soluble thrombomodulin with major bleeding in the BLEEDS cohort, a cohort especially powered to find new biomarkers of major bleeding during VKA therapy.

Methods

To determine and compare the predictive capability for major bleeding in the BLEEDS cohort of the above biomarkers, also in a combined model with clinical risk factors, we performed Univariable Prentice-weighted Cox regression analyses and Bayesian variable selection.

Results

The highest predictive value among the laboratory measures were found for thrombin generation lagtime in the presence of TIX-5 (TIX-5 lagtime per 25% increase, hazard ratio (HR) 1.11, 95%CI 1.04–1.18, p=0.001) and full-length tissue factor pathway inhibitor (TFPIα) (per 25% increase HR 1.12, 95%CI 1.03–1.21, p=0.008), which remained significant after correction for multiple testing, and independently associated with major bleeding after Bayesian variable selection. Only the addition of TIX-5 lagtime to the clinical risk factors improved prediction of major bleeding significantly (p<0.001).

Conclusion

We established predictive value of the lagtime of thrombin generation measured in the presence of TIX-5 for the risk of a major bleeding of patients on VKA therapy.

Background

Type 2 diabetes mellitus (T2DM) and atrial fibrillation are risk factors for stroke. The potential preventive effects of cardiovascular and antidiabetic treatments on stroke risk in patients with these diseases remain insufficiently documented. Sulfonylureas have also been reported to be associated with stroke. This study aimed to assess the risk of stroke according to the use of drugs (anticoagulants, antiplatelet agents, and oral antidiabetic drugs [OADs]) in patients with T2DM and nonvalvular atrial fibrillation (NVAF).

Methods

Patients with a history of T2DM and NVAF were identified from two systematic registries: a registry of patients with stroke and a registry of patients with atrial fibrillation. Patients with stroke were randomly matched to patients without prior stroke events based on age, sex, body mass index, and index date. All treatments administered 12 months before the index date were documented. The associations between anticoagulants, antiplatelet agents, and OADs and stroke were assessed using multivariate conditional logistic models that yielded adjusted odds ratios (aORs) and 95 % confidence intervals, controlling for risk factors identified in the univariate comparison of cases and matched referents.

Results

Three-hundred and fifteen patients with stroke with both diabetes and NVAF were matched to 523 referents with both diabetes and NVAF but no history of stroke. The aORs for the use of drugs and stroke were 0.24 [0.15–0.40] for direct oral anticoagulants (DOACs), 0.42 [0.27–0.67] for vitamin K agonists (VKA), 0.80 [0.52–1.24] for antiplatelet agents, and 0.68 [0.45–1.02] for OADs. No significant associations were found between individual OAD use and stroke risk. Similar results were obtained for ischemic stroke. Only VKAs were significantly associated with hemorrhagic stroke (odds ratio = 4.25 [1.16–15.64]).

Conclusions

Anticoagulant use was associated with a protective effect against the risk of stroke in patients with diabetes and NVAF, with no increase in the risk of hemorrhagic stroke for DOAC. No increased risk of stroke was observed because of any OAD, including sulfonylureas.

Thrombotic microangiopathies during pregnancy are rare but may be life-threatening diseases for both the mother and the fetus. Thrombotic thrombocytopenic purpura (TTP) patients present with hemolytic anemia and thrombocytopenia associated with low ADAMTS-13 activity, a cleaving von Willebrand factor protein. Pregnancy has been described not only as a trigger of TTP but also as a phenotype modifier. In addition, hormonal changes induced by assisted reproduction technology (ART) swift the thrombotic – thrombolytic state towards coagulation, while increasing the pregnancy complications’ rate. We present a case of a 34-year-old pregnant woman, who conceived via ART and diagnosed with TTP at 13 weeks of gestation. She was initially treated with corticosteroids and daily plasmapheresis. Due to gradual unresponsiveness to treatment, rituximab was also added. After 3 doses, she was diagnosed with mild ovarian hyperstimulation syndrome, which resolved spontaneously after several weeks. She delivered a healthy neonate at 39⁺¹ weeks via emergency cesarean section due to fetal distress, while the postpartum follow-up was uneventful. In conclusion, TTP should be suspected to a pregnant woman with raised hemorrhagic risk presenting with hematuria, anemia and thrombocytopenia.

The incidence of venous thromboembolism (VTE) in cancer patients is 4–9 fold higher compared with the general population. The mortality rate of patients with cancer and VTE is more than 2-fold greater versus cancer patients without VTE. Given that the pathophysiology of thrombosis in cancer is multi-faceted, investigations of the mechanisms that regulate cancer-associated thrombosis (CAT) could improve the understanding and treatment of CAT. These mechanisms include activation of the coagulation and fibrinolytic systems. Tumor cells activate coagulation by expressing procoagulant molecules, releasing pro-inflammatory and pro-angiogenic cytokines, and adhering to vascular and blood cells. Tumor-secreted and tissue factor-positive extracellular vesicles are another major driver of CAT, while emerging studies have discovered a role for podoplanin (PDPN) in intratumoral thrombosis, hyper-coagulation, and enhanced VTE risk. In this article, we will review studies of PDPN in CAT, which together suggest that PDPN contributes not only to cancer progression and metastasis, but also to CAT. PDPN may therefore represent an attractive putative target for therapies that aim to simultaneously reduce cancer progression and associated VTE.

Anticoagulant therapy has always been tightly connected with bleeding risk, as two sides of the same coin. New insights in thrombosis and hemostasis prompted the development of intrinsic pathway inhibitors that promise to uncouple thrombosis and hemostasis. Treating and preventing thrombotic complications without the associated bleeding risk opens up many new possibilities for patients with an unmet need with the current anticoagulant drugs. Many candidate drugs are being investigated in phase I, II, and III clinical trials. In this review, we will introduce the new insights driving this evolution in drug development, whereafter the drugs under development and their clinical trials will be discussed.